Objective To investigate the abnormal changes characteristics of the degree centrality(DC)of the brain functional network in patients with benign paroxysmal positional vertigo(BPPV)in the classical frequency band(0.010-0.080 Hz),the slow-4 frequency band(0.027-0.073 Hz),and the slow-5 frequency band(0.010-0.027 Hz).Methods Twenty patients with BPPV(BPPV group)and 14 healthy controls(HC)(HC group)were selected.Resting-state functional magnetic resonance imaging(rs-fMRI)scans were performed,and the clinical data were analyzed.The DC method was used to analyze the changes of centrality of resting state network in patients with BPPV.Results Compared with the HC group,the BPPV group showed an increase in DC in the left caudate nucleus in the classical frequency band(P＜0.05),and a decrease in DC in the right auxiliary motor region in the classical frequency band(P＜0.05);within the slow-4 frequency band,no significant differences were observed in brain regions(P＞0.05);within the slow-5 frequency band,the BPPV group showed an increase in DC in the left thalamus(P＜0.05),while the left anterior cingulate and paracingulate gyrus showed a decrease in DC(P＜0.05).Conclusion Patients with BPPV have spontaneous activity disorders in multiple brain regions at resting states,and these changes show frequency band specificity.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective To investigate the role and molecular mechanism of ginsenoside Rb1(Rb1)in regulating neutrophil extracellular trapping networks(NETs)to intervene in atherosclerosis(AS).Methods In vivo:an AS model was constructed with ApoE knockout mice superimposed on a high-fat diet.The pathological and morphological changes of aortic root plaques were observed by HE staining and oil red O staining;Immunofluorescence labelling of neutrophils citrullinated histones(Cit-H3)and macrophages as well as IL-1β at the aortic root plaque site were used to assess the inflammatory infiltration.In vitro:NETs induced by PMA and cholesterol crystals were taken as models respectively.Direct effect of Rb1 against NETs formation assessed by Sytox staining and immunofluorescence staining with Cit-H3 and myeloperoxidase.Rb1 on ROS levels was assessed by DCFH-DA.Rb1 on histone H3 citrulline modification was assessed by Western blotting.Results In vivo:Rb1 significantly inhibited plaque formation,lipid deposition(P<0.05)and intra-plaque inflammatory infiltration(P<0.05).In vitro:Rb1 significantly inhibited NETs formation(P<0.05),neutrophil ROS levels(P<0.05),and Cit-H3 levels(P<0.05).Conclusions Rb1 significantly inhibited AS progression by inhibiting plaque NETs formation,which may be partly through the inhibition of histone H3 citrullination resulting from activation of the neutrophil oxidative stress pathway.

Objective To investigate the role and molecular mechanism of ginsenoside Rb1(Rb1)in regulating neutrophil extracellular trapping networks(NETs)to intervene in atherosclerosis(AS).Methods In vivo:an AS model was constructed with ApoE knockout mice superimposed on a high-fat diet.The pathological and morphological changes of aortic root plaques were observed by HE staining and oil red O staining;Immunofluorescence labelling of neutrophils citrullinated histones(Cit-H3)and macrophages as well as IL-1β at the aortic root plaque site were used to assess the inflammatory infiltration.In vitro:NETs induced by PMA and cholesterol crystals were taken as models respectively.Direct effect of Rb1 against NETs formation assessed by Sytox staining and immunofluorescence staining with Cit-H3 and myeloperoxidase.Rb1 on ROS levels was assessed by DCFH-DA.Rb1 on histone H3 citrulline modification was assessed by Western blotting.Results In vivo:Rb1 significantly inhibited plaque formation,lipid deposition(P<0.05)and intra-plaque inflammatory infiltration(P<0.05).In vitro:Rb1 significantly inhibited NETs formation(P<0.05),neutrophil ROS levels(P<0.05),and Cit-H3 levels(P<0.05).Conclusions Rb1 significantly inhibited AS progression by inhibiting plaque NETs formation,which may be partly through the inhibition of histone H3 citrullination resulting from activation of the neutrophil oxidative stress pathway.

Objective To investigate the abnormal changes characteristics of the degree centrality(DC)of the brain functional network in patients with benign paroxysmal positional vertigo(BPPV)in the classical frequency band(0.010-0.080 Hz),the slow-4 frequency band(0.027-0.073 Hz),and the slow-5 frequency band(0.010-0.027 Hz).Methods Twenty patients with BPPV(BPPV group)and 14 healthy controls(HC)(HC group)were selected.Resting-state functional magnetic resonance imaging(rs-fMRI)scans were performed,and the clinical data were analyzed.The DC method was used to analyze the changes of centrality of resting state network in patients with BPPV.Results Compared with the HC group,the BPPV group showed an increase in DC in the left caudate nucleus in the classical frequency band(P＜0.05),and a decrease in DC in the right auxiliary motor region in the classical frequency band(P＜0.05);within the slow-4 frequency band,no significant differences were observed in brain regions(P＞0.05);within the slow-5 frequency band,the BPPV group showed an increase in DC in the left thalamus(P＜0.05),while the left anterior cingulate and paracingulate gyrus showed a decrease in DC(P＜0.05).Conclusion Patients with BPPV have spontaneous activity disorders in multiple brain regions at resting states,and these changes show frequency band specificity.

Objective:To investigate the effect of astragaloside A (AS-A) on the photoreceptor degeneration induced by sodium iodate (NaIO 3) and its related mechanism. Methods:Sixty healthy male C57BL/6J mice, aged 6-8 weeks, were randomly divided into normal control (NC) group, NaIO 3 group, and ASA group, with twenty mice in each group. 30 min before modeling, AS-A group mice were intraperitoneally injected with 100 μl AS-A at a dose of 100 mg/kg body weight. 30 min later, mice in NaIO 3 group and AS-A group were intraperitoneally injected with 100 μl NaIO 3 at a dose of 30 mg/kg body weight. Subsequently, AS-A group mice were administered AS-A twice daily at 12 h intervals until the end of the experiment. On day 1 post-modeling, zonula occludens-1 (ZO-1) immunohistochemistry was performed to observe the structure of retinal pigment epithelium (RPE) cells; real-time quantitative polymerase chain reaction (qPCR) was conducted to detect the mRNA expression of various retinal chemokine ligand-2 ( Ccl2), interleukin-1 beta ( Il-1β), mixed lineage kinase domain-like protein ( Mlkl), receptor-interacting protein kinase 3 ( Ripk3), and tumor necrosis factor ( Tnf). On day 3 post-modeling, immunohistochemistry was performed to observe the expression of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acid protein (GFAP) in the retina; TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to detect photoreceptor cell death in each group. On day 4 post-modeling, fundus morphology of mice in each group was observed by fundus color photography and optical coherence tomography (OCT). Hematoxylin-eosin staining (HE) was used to observe the morphological structure of the retina in each group. Inter-group comparisons between two groups were conducted using independent samples t-test, while comparisons among three groups were performed using one-way ANOVA. Results:Fundus color photography and OCT examination showed that a large number of scattered yellow-white subretinal nodular structures in the fundus of NaIO 3 group mice, and a large number of strong reflection areas in the RPE layer. The number of strong reflection areas in the RPE layer was reduced in the AS-A group. Immunohistochemical analysis of ZO-1 showed that ZO-1 was largely lost on the RPE cell membrane in that NaIO 3 group; whereas in the AS-A group, ZO-1 was evenly distributed on the RPE cell membrane. HE staining results showed circular black deposits were visible in the RPE layer of the NaIO 3 group, and the inner and outer segments of photoreceptors were severely damaged, with a significant decrease in the number of outer nuclear layer (ONL) cell nuclei; whereas in the AS-A group, the RPE layer pigments were orderly, the inner and outer segments of photoreceptors were intact, and the number of ONL cell nuclei significantly increased. The results of TUNEL staining show that numerous TUNEL-positive cell nuclei were observed in the ONL of the retina in the NaIO 3 group, while the number of TUNEL-positive cell nuclei in the ONL of the retina was significantly reduced in the AS-A group, with statistically significant differences ( t=2.66, P<0.05). The analysis of qPCR data showed that compared with the AS-A group, the relative expression levels of Mlkl, Ripk3, Ccl2, Il-1β and Tnf mRNA in the retina were significantly increased in the NaIO 3 group, with statistically significant differences ( F=39.18, 10.66, 53.51, 41.40, 24.13; P<0.001). Immunohistochemical staining results showed that compared with NC group and AS-A group, the positive expression of GFAP in retina of NaIO 3 group was significantly increased, and the difference was statistically significant ( F=9.62, P<0.05). Conclusion:AS-A antagonizes NaIO 3-induced photoreceptor degeneration in part by inhibiting photoreceptor cell death and neuroinflammation. Meanwhile, AS-A treatment protects against NaIO 3-triggered perturbation of retinal homeostasis.

Objective The current study aims to investigate the protective effect and mechanisms of baicalin on pathological left ventricular remodeling.Methods Angiotensin Ⅱ(Ang Ⅱ)infusion mouse model was adopted to evaluate the impact of baicalin on pathological left ventricular remodeling in vivo.C57BL/6J mice were randomly allocated to 5 experimental groups,including sham controls,model group(Ang Ⅱ-infusion controls),as well as low-,medium-,and high-dose baicalin treatment groups.Except for the sham controls,C57/BL6 mice were subjected to AngⅡ infusion for 2 weeks.The mice from the baicalin treatment groups received baicalin via gavage at the indicated doses for 2 weeks.The blood pressure,body weight,heart weight and tibia length were measured at the end of the indicated treatments.Immunohistochemistry of wheat germ agglutinin(WGA)was performed to examine the cross-sectional area of cardiomyocytes.Immunohistochemistry was also performed to assess the expression of atrial natriuretic peptide(ANP)in cardiomyocytes.Hematoxylin/eosin(HE)staining and Masson's trichrome staining were performed to evaluate the cardiac pathologies.In vitro experiments were as follows.Ang Ⅱ was adopted to induce cardiomyocyte hypertrophy in H9C2 cells in order to determine if baicalin is able to directly suppress cardiomyocyte hypertrophy.H9C2 cells were divided into vehicle control group(VC group),model group(Ang Ⅱ group)and baicalin group(Bai group).The morphology and size of cardiomyocytes were examined by rhodamine phalloidin staining.The intracellular level of ANP was analyze by immunofluorescence staining.Mitochondrial superoxide(Mito-SOX)was assessed to evaluate oxidative stress.The mitochondrial membrane potential(ΔΨm)was analyzed by JC-1 staining.The opening of mitochondrial permeability transition pore(mPTP)was evaluated by calcein acetyl methyl ester(Calcein AM)staining.Results The in vivo findings:Baicalin significantly antagonized Ang Ⅱ-induced elevation of systolic blood pressure(P<0.05)when administered at the medium and high doses.Meanwhile,baicalin treatment resulted in lower ratios of heart weight to tibia length(HW/TL)and heart weight to body weight(HW/BW)in Ang Ⅱ-infused mice.Baicalin treatment mitigated cardiomyocyte hypertrophy(P<0.05)and lowered the level of cardiomyocyte ANP(P<0.05)in Ang Ⅱ-infused mice.Furthermore,baicalin treatment significantly alleviated cardiac inflammation and fibrosis in Ang Ⅱ-infused mice(P<0.05).In vitro findings:Baicalin suppressed Ang Ⅱ-stimulated enlargement of cardiomyocytes and elevation of the intracellular ANP in H9C2 cells.Moreover,baicalin alleviated Ang Ⅱ-induced mitochondrial oxidative stress,mitochondrial ΔΨm impairment and mPTP opening(P<0.05).Conclusion Our current findings demonstrate that baicalin is effective at mitigating Ang Ⅱ-mediated left ventricular pathological remodeling.Baicalin is pharmacologically active at antagonizing Ang Ⅱ-induced hypertrophic responses and mitochondrial dysfunction in cardiomyocytes,which may in part account for its therapeutic effects against pathological left ventricular remodeling.

Objective The current study aims to investigate the protective effect and mechanisms of baicalin on pathological left ventricular remodeling.Methods Angiotensin Ⅱ(Ang Ⅱ)infusion mouse model was adopted to evaluate the impact of baicalin on pathological left ventricular remodeling in vivo.C57BL/6J mice were randomly allocated to 5 experimental groups,including sham controls,model group(Ang Ⅱ-infusion controls),as well as low-,medium-,and high-dose baicalin treatment groups.Except for the sham controls,C57/BL6 mice were subjected to AngⅡ infusion for 2 weeks.The mice from the baicalin treatment groups received baicalin via gavage at the indicated doses for 2 weeks.The blood pressure,body weight,heart weight and tibia length were measured at the end of the indicated treatments.Immunohistochemistry of wheat germ agglutinin(WGA)was performed to examine the cross-sectional area of cardiomyocytes.Immunohistochemistry was also performed to assess the expression of atrial natriuretic peptide(ANP)in cardiomyocytes.Hematoxylin/eosin(HE)staining and Masson's trichrome staining were performed to evaluate the cardiac pathologies.In vitro experiments were as follows.Ang Ⅱ was adopted to induce cardiomyocyte hypertrophy in H9C2 cells in order to determine if baicalin is able to directly suppress cardiomyocyte hypertrophy.H9C2 cells were divided into vehicle control group(VC group),model group(Ang Ⅱ group)and baicalin group(Bai group).The morphology and size of cardiomyocytes were examined by rhodamine phalloidin staining.The intracellular level of ANP was analyze by immunofluorescence staining.Mitochondrial superoxide(Mito-SOX)was assessed to evaluate oxidative stress.The mitochondrial membrane potential(ΔΨm)was analyzed by JC-1 staining.The opening of mitochondrial permeability transition pore(mPTP)was evaluated by calcein acetyl methyl ester(Calcein AM)staining.Results The in vivo findings:Baicalin significantly antagonized Ang Ⅱ-induced elevation of systolic blood pressure(P<0.05)when administered at the medium and high doses.Meanwhile,baicalin treatment resulted in lower ratios of heart weight to tibia length(HW/TL)and heart weight to body weight(HW/BW)in Ang Ⅱ-infused mice.Baicalin treatment mitigated cardiomyocyte hypertrophy(P<0.05)and lowered the level of cardiomyocyte ANP(P<0.05)in Ang Ⅱ-infused mice.Furthermore,baicalin treatment significantly alleviated cardiac inflammation and fibrosis in Ang Ⅱ-infused mice(P<0.05).In vitro findings:Baicalin suppressed Ang Ⅱ-stimulated enlargement of cardiomyocytes and elevation of the intracellular ANP in H9C2 cells.Moreover,baicalin alleviated Ang Ⅱ-induced mitochondrial oxidative stress,mitochondrial ΔΨm impairment and mPTP opening(P<0.05).Conclusion Our current findings demonstrate that baicalin is effective at mitigating Ang Ⅱ-mediated left ventricular pathological remodeling.Baicalin is pharmacologically active at antagonizing Ang Ⅱ-induced hypertrophic responses and mitochondrial dysfunction in cardiomyocytes,which may in part account for its therapeutic effects against pathological left ventricular remodeling.

To investigate the effect and mechanism of metformin on intestinal epithelial barrier injury in ulcerative colitis. A cell model of colitis was established by co-culture of human colon cancer cell line Caco-2 and human monocyte cell line THP-1. The colitis model cells were treated with metformin at concentration of for Flow cytometry was used to detect Caco-2 cell apoptosis, and Western blotting was used to detect the protein expression of tight junction proteins and endoplasmic reticulum stress-related proteins. After metformin treatment, the apoptosis rate of Caco-2 cells was decreased from (14.22±2.34)% to 0.61)% (=3.119, <0.05), and the expression levels of tight junction protein-1 and claudin-1 increased (=5.172 and 3.546, both <0.05). In addition, the expression levels of endoplasmic reticulum-related proteins glucose regulated protein (GRP) 78, C/EBP homologous protein (CHOP) and caspase-12, as well as the phosphorylation level of PRKR-like endoplasmic reticulum kinase (PERK) and eukaryotic translation initiation factor 2α (eIF2α) decreased (all <0.05). Metformin may alleviate the intestinal epithelial barrier damage in colitis by reducing intestinal epithelial cell apoptosis and increasing the expression of tight junction proteins, which may be associated with the inhibition of endoplasmic reticulum stress-induced apoptotic pathway.
Apoptosis ; Caco-2 Cells ; Colitis, Ulcerative ; Endoplasmic Reticulum Stress ; Humans ; Metformin/pharmacology*